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RENAL FUNCTION TESTS
KOOME IMPWII
KIDNEY FUNCTIONS
 Maintenance of homeostasis: responsible for water,
electrolyte and acid-base balance
 Excretion of metabolic waste products: end
products of protein and nucleic acids e.g. urea,
creatinine, uric acid etc.
 Retention of substances vital to the body: glucose,
amino acids etc.
 Hormonal function: Erythropoietin, calcitriol, renin
etc
10-May-16
2
ClinicalChemistry
 kidneys use ¼ of the total cardiac output
 Produce 180 l/day (or 125 ml/min) of glomerular
filtrate.
 Each kidney has about 1 million nephrons.
10-May-16
3
ClinicalChemistry
URINE FORMATION
 Glomerular filtration: formation of ultrafiltrate
 waste materials of plasma are filtered
 Tubular reabsorption: formation of pure urine
 PCT & DCT retain water and most of the soluble
constituents of the glomerular filtrate by reabsorption
10-May-16
4
ClinicalChemistry
RENAL THRESHOLD
 Renal threshold of a substance is the concentration
in blood beyond which it is excreted in urine
 Renal threshold for glucose is 180mg/dL
10-May-16
5
ClinicalChemistry
TUBULAR MAXIMUM
 Tubular maximum (Tm): maximum capacity of the
kidneys to absorb a particular substance
 Tm for glucose is 350 mg/min
10-May-16
6
ClinicalChemistry
RENAL FUNCTION TESTS
 Performed to:
 Identify renal dysfunction.
 Diagnose renal disease.
 Monitor disease progress.
 Monitor response to treatment.
 Assess changes in function that may impact on therapy
(e.g. Digoxin, chemotherapy).
10-May-16
7
ClinicalChemistry
WHEN SHOULD YOU ASSESS RENAL
FUNCTION
 Older age
 Family history of Chronic Kidney disease (CKD)
 Decreased renal mass
 Low birth weight
 Diabetes Mellitus (DM)
 Hypertension (HTN)
 Autoimmune disease
 Systemic infections
 Urinary tract infections (UTI)
 Nephrolithiasis
 Obstruction to the lower urinary tract
 Drug toxicity
10-May-16
8
ClinicalChemistry
WHEN SHOULD YOU ASSESS RENAL
FUNCTION?
 Older age
 Family history of Chronic Kidney disease (CKD)
 Decreased renal mass
 Low birth weight
 Diabetes Mellitus (DM)
 Hypertension (HTN)
 Autoimmune disease
 Systemic infections
 Urinary tract infections (UTI)
 Nephrolithiasis
 Obstruction to the lower urinary tract
 Drug toxicity
10-May-16
9
ClinicalChemistry
BIOCHEMICAL TESTS OF RENAL FUNCTION
 Measurement of GFR
 Renal tubular Function Tests
 Urinalysis
10-May-16
10
ClinicalChemistry
MEASUREMENTS OF GFR
Clearance tests
Plasma creatinine
Urea, uric acid and β2-
microglobulin
10-May-16
11
ClinicalChemistry
RENAL TUBULAR FUNCTION TESTS
 Osmolality measurements
 Specific proteinurea
 Glycouria
 Aminoaciduria
10-May-16
12
ClinicalChemistry
URINALYSIS
 Appearance
 Specific gravity and osmolality
 pH
 osmolality
 Glucose
 Protein
 Urinary sediments
10-May-16
13
ClinicalChemistry
MEASUREMENT OF GFR
 GFR is essential to renal function
 Most frequently performed test of renal function.
 Measurement is based on concept of clearance: -
“The determination of the volume of plasma from
which a substance is removed by glomerular
filtration during it’s passage through the kidney”
10-May-16
14
ClinicalChemistry
DETERMINATION OF CLEARANCE
 Clearance = (UxV)/P
Where, U is the urinary concentration of
substance
V is the rate of urine formation (mL/min)
P is the plasma concentration of
substance
 Units = volume/unit time (mL/min)
10-May-16
15
ClinicalChemistry
IDEAL SUBSTANCE FOR MEASURING GFR
 Freely filtered by glomerulus
 Glomerulus is sole route of excretion from the body
(no tubular secretion or reabsorbtion)
 Non-toxic
 Easily measurable
 Not protein bound
 Has a constant endogenous production rate
10-May-16
16
ClinicalChemistry
PROPERTIES OF AGENTS USED TO DETERMINE
GFR
Property Urea Creatinine Inulin
Not Protein
Bound
Yes Yes Yes
Freely Filtered Yes Yes Yes
No secretion or
absorbtion
Flow related
reabsorption
Some secretion Yes
Constant
endogenous
production rate
No Yes No
Easily Assayed Yes Yes No
10-May-16 17Clinical Chemistry
CREATININE
 1 to 2% of muscle creatine spontaneously converts to
creatinine daily and released into body fluids at a constant
rate.
 Endogenous creatinine produced is proportional to muscle
mass, it is a function of total muscle mass the production
varies with age and sex
 Dietary fluctuations of creatinine intake cause only minor
variation in daily creatinine excretion of the same person.
 Creatinine released into body fluids at a constant rate and its
plasma levels maintained within narrow limits  Creatinine
clearance may be measured as an indicator of GFR.
10-May-16
18
ClinicalChemistry
CREATININE CLEARANCE
An estimate of the GFR can be calculated from the
creatinine content of a 24-hour urine collection, and
the plasma concentration within this period.
The volume of urine is measured, urine flow rate is
calculated (ml/min) and the assay for creatinine is
performed on plasma and urine to obtain the
concentration in mg per dl or per ml.
 Normal range = 120ml/min
10-May-16
19
ClinicalChemistry
10-May-16
20
ClinicalChemistry
The 'clearance' of creatinine from plasma is directly
related to the GFR if:
 The urine volume is collected accurately
 There are no ketones or heavy proteinuria present to interfere with
the creatinine determination.
It should be noted that the GFR decline with age (to
a greater extent in males than in females) and this
must be taken into account when interpreting results.
10-May-16
21
ClinicalChemistry
BLOOD UREA
 Derived from the liver through protein breakdown
 Major nitrogen-containing metabolic product of protein
catabolism in humans,
 Its elimination in the urine represents the major route
for nitrogen excretion.
 More than 90% of urea is excreted through the kidneys,
with losses through the GIT and skin
 Urea is filtered freely by the glomeruli
 About 30-40% normally reabsorbed in tubules
 Plasma urea concentration is often used as an index of
renal glomerular function
10-May-16
22
ClinicalChemistry
Urea production is increased by
 high protein intake
 Catabolic states-muscle wasting as in starvation
 Post surgery and trauma
 GIT bleeding-reabsorption of blood protein
 Dehydration
 Urinary Stasis
10-May-16
23
ClinicalChemistry
 Decreased in
 patients with a low protein intake
 patients with liver disease
 Dialysis (urea crosses dialysis membrane easier)
10-May-16
24
ClinicalChemistry
UREMIA/ AZOTEMIA
 States associated with elevated levels of urea in
blood
 Plasma concentration increases with reduced
GFR
 Causes of urea plasma elevations:
 Prerenal: renal hypoperfusion
 Renal: acute tubular necrosis
 Postrenal: obstruction of urinary flow
10-May-16
25
ClinicalChemistry
TUBULAR FUNCTION TESTS
 Urinary Na+ concentration. Normally low relative to
serum concentration unless on a dietary high salt
intake.
 Concentration tests (usually after Pitressin), and
Dilution tests, after a water load.
 Acidification tests, after administration of NH4Cl (
→ NH3 + H+ + Cl- ). Seldom done except in
differentiation of type I and II renal tubular
acidoses
10-May-16
26
ClinicalChemistry
RENAL CONCENTRATION TEST
 Voiding completely at 9 p.m. (WC)
 Desmopressin administration
 Collection of urine (9 p.m. – 7 a.m.)
 Testing of urine osmolality in this sample (not the
morning urine only
 The lower limit of normal value= 950
mOsm/kg of urine
 Short testing- Desmopressin, collection for 4
hours only= at least 900 mOsm/kg of urine
10-May-16
27
ClinicalChemistry
URINALYSIS
 Appearance
 Specific gravity and osmolality
 pH
 Glucose
 Protein
 Urinary sediments?
10-May-16
28
ClinicalChemistry
PROTEIN
 > 2.5 g/day indicates nephrotic syndrome, Bence-
Jones Protein indicates myeloma , ß2-
microglobulin, small protein, filtered then absorbed
by tubules, which is a sensitive test of tubular
function (but also ↑ in some malignancies and
inflammatory conditions).
10-May-16
29
ClinicalChemistry
DISEASES
 Nephrotic Syndrome
 Acute Renal failure
 Water diuresis
 Osmotic diuresis
10-May-16
30
ClinicalChemistry
NEPHROTIC SYNDROME
 Increased permeability of glomerulus to proteins
with proteinuria greater than 2.5 g/day with:
 Edema
 Hypoproteinuria
 Increased serum lipids
10-May-16
31
ClinicalChemistry
ACUTE RENAL FAILURE
 Urine output <450 ml/day with a rising urea
 May be:
 Pre-renal failure (defect before the kidney)
 Intra-renal failure (defect in the kidney e.g. acute
tubular necrosis, glomerulonephritis)
 Post-renal failure (defect after the kidney, e.g. prostatic
enlargement, urolithiasis).
10-May-16
32
ClinicalChemistry
ACUTE RENAL FAILURE
Metabolic features:
 Retention of:
 Urea & creatinine
 Na & water
 potassium with hyper-
kalaemia
 Acid with metabolic
acidosis
Classification of Causes:
 Pre-renal
 reduced perfusion
 Renal
 inflammation
 infiltration
 toxicity
 Post-renal
 obstruction
10-May-16
33
ClinicalChemistry
Prerenal Intrarenal
Urine sodium
Conc
<20mmol?L >40 mmol/L
Urine/plasma
osmolarity
ratio
>1.4 <1.1
Urine/plasma
urea ratio
>14 <10
10-May-16
34
ClinicalChemistry
WATER DIURESIS
 urinary osmolality <200
 Caused by:
 Compulsive water drinking
 Diabetes insipidus - neurogenic or nephrogenic
10-May-16
35
ClinicalChemistry
OSMOTIC DIURESIS
 urinary osmolality + 300
 Caused by the presence of incompletely
reabsorbed solutes in the tubular lumen:
 Na+ - dietary, iatrogenic, diuretics, salt-losing nephritis.
 Urea – CRF, recovery phase of acute tubular necrosis
or post-renal failure
 Glucose (diabetes mellitus)
 Mannitol,and some other therapeutic agents.
10-May-16
36
ClinicalChemistry
THE END
10-May-16
37
ClinicalChemistry

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Renal function tests

  • 2. KIDNEY FUNCTIONS  Maintenance of homeostasis: responsible for water, electrolyte and acid-base balance  Excretion of metabolic waste products: end products of protein and nucleic acids e.g. urea, creatinine, uric acid etc.  Retention of substances vital to the body: glucose, amino acids etc.  Hormonal function: Erythropoietin, calcitriol, renin etc 10-May-16 2 ClinicalChemistry
  • 3.  kidneys use ¼ of the total cardiac output  Produce 180 l/day (or 125 ml/min) of glomerular filtrate.  Each kidney has about 1 million nephrons. 10-May-16 3 ClinicalChemistry
  • 4. URINE FORMATION  Glomerular filtration: formation of ultrafiltrate  waste materials of plasma are filtered  Tubular reabsorption: formation of pure urine  PCT & DCT retain water and most of the soluble constituents of the glomerular filtrate by reabsorption 10-May-16 4 ClinicalChemistry
  • 5. RENAL THRESHOLD  Renal threshold of a substance is the concentration in blood beyond which it is excreted in urine  Renal threshold for glucose is 180mg/dL 10-May-16 5 ClinicalChemistry
  • 6. TUBULAR MAXIMUM  Tubular maximum (Tm): maximum capacity of the kidneys to absorb a particular substance  Tm for glucose is 350 mg/min 10-May-16 6 ClinicalChemistry
  • 7. RENAL FUNCTION TESTS  Performed to:  Identify renal dysfunction.  Diagnose renal disease.  Monitor disease progress.  Monitor response to treatment.  Assess changes in function that may impact on therapy (e.g. Digoxin, chemotherapy). 10-May-16 7 ClinicalChemistry
  • 8. WHEN SHOULD YOU ASSESS RENAL FUNCTION  Older age  Family history of Chronic Kidney disease (CKD)  Decreased renal mass  Low birth weight  Diabetes Mellitus (DM)  Hypertension (HTN)  Autoimmune disease  Systemic infections  Urinary tract infections (UTI)  Nephrolithiasis  Obstruction to the lower urinary tract  Drug toxicity 10-May-16 8 ClinicalChemistry
  • 9. WHEN SHOULD YOU ASSESS RENAL FUNCTION?  Older age  Family history of Chronic Kidney disease (CKD)  Decreased renal mass  Low birth weight  Diabetes Mellitus (DM)  Hypertension (HTN)  Autoimmune disease  Systemic infections  Urinary tract infections (UTI)  Nephrolithiasis  Obstruction to the lower urinary tract  Drug toxicity 10-May-16 9 ClinicalChemistry
  • 10. BIOCHEMICAL TESTS OF RENAL FUNCTION  Measurement of GFR  Renal tubular Function Tests  Urinalysis 10-May-16 10 ClinicalChemistry
  • 11. MEASUREMENTS OF GFR Clearance tests Plasma creatinine Urea, uric acid and β2- microglobulin 10-May-16 11 ClinicalChemistry
  • 12. RENAL TUBULAR FUNCTION TESTS  Osmolality measurements  Specific proteinurea  Glycouria  Aminoaciduria 10-May-16 12 ClinicalChemistry
  • 13. URINALYSIS  Appearance  Specific gravity and osmolality  pH  osmolality  Glucose  Protein  Urinary sediments 10-May-16 13 ClinicalChemistry
  • 14. MEASUREMENT OF GFR  GFR is essential to renal function  Most frequently performed test of renal function.  Measurement is based on concept of clearance: - “The determination of the volume of plasma from which a substance is removed by glomerular filtration during it’s passage through the kidney” 10-May-16 14 ClinicalChemistry
  • 15. DETERMINATION OF CLEARANCE  Clearance = (UxV)/P Where, U is the urinary concentration of substance V is the rate of urine formation (mL/min) P is the plasma concentration of substance  Units = volume/unit time (mL/min) 10-May-16 15 ClinicalChemistry
  • 16. IDEAL SUBSTANCE FOR MEASURING GFR  Freely filtered by glomerulus  Glomerulus is sole route of excretion from the body (no tubular secretion or reabsorbtion)  Non-toxic  Easily measurable  Not protein bound  Has a constant endogenous production rate 10-May-16 16 ClinicalChemistry
  • 17. PROPERTIES OF AGENTS USED TO DETERMINE GFR Property Urea Creatinine Inulin Not Protein Bound Yes Yes Yes Freely Filtered Yes Yes Yes No secretion or absorbtion Flow related reabsorption Some secretion Yes Constant endogenous production rate No Yes No Easily Assayed Yes Yes No 10-May-16 17Clinical Chemistry
  • 18. CREATININE  1 to 2% of muscle creatine spontaneously converts to creatinine daily and released into body fluids at a constant rate.  Endogenous creatinine produced is proportional to muscle mass, it is a function of total muscle mass the production varies with age and sex  Dietary fluctuations of creatinine intake cause only minor variation in daily creatinine excretion of the same person.  Creatinine released into body fluids at a constant rate and its plasma levels maintained within narrow limits  Creatinine clearance may be measured as an indicator of GFR. 10-May-16 18 ClinicalChemistry
  • 19. CREATININE CLEARANCE An estimate of the GFR can be calculated from the creatinine content of a 24-hour urine collection, and the plasma concentration within this period. The volume of urine is measured, urine flow rate is calculated (ml/min) and the assay for creatinine is performed on plasma and urine to obtain the concentration in mg per dl or per ml.  Normal range = 120ml/min 10-May-16 19 ClinicalChemistry
  • 21. The 'clearance' of creatinine from plasma is directly related to the GFR if:  The urine volume is collected accurately  There are no ketones or heavy proteinuria present to interfere with the creatinine determination. It should be noted that the GFR decline with age (to a greater extent in males than in females) and this must be taken into account when interpreting results. 10-May-16 21 ClinicalChemistry
  • 22. BLOOD UREA  Derived from the liver through protein breakdown  Major nitrogen-containing metabolic product of protein catabolism in humans,  Its elimination in the urine represents the major route for nitrogen excretion.  More than 90% of urea is excreted through the kidneys, with losses through the GIT and skin  Urea is filtered freely by the glomeruli  About 30-40% normally reabsorbed in tubules  Plasma urea concentration is often used as an index of renal glomerular function 10-May-16 22 ClinicalChemistry
  • 23. Urea production is increased by  high protein intake  Catabolic states-muscle wasting as in starvation  Post surgery and trauma  GIT bleeding-reabsorption of blood protein  Dehydration  Urinary Stasis 10-May-16 23 ClinicalChemistry
  • 24.  Decreased in  patients with a low protein intake  patients with liver disease  Dialysis (urea crosses dialysis membrane easier) 10-May-16 24 ClinicalChemistry
  • 25. UREMIA/ AZOTEMIA  States associated with elevated levels of urea in blood  Plasma concentration increases with reduced GFR  Causes of urea plasma elevations:  Prerenal: renal hypoperfusion  Renal: acute tubular necrosis  Postrenal: obstruction of urinary flow 10-May-16 25 ClinicalChemistry
  • 26. TUBULAR FUNCTION TESTS  Urinary Na+ concentration. Normally low relative to serum concentration unless on a dietary high salt intake.  Concentration tests (usually after Pitressin), and Dilution tests, after a water load.  Acidification tests, after administration of NH4Cl ( → NH3 + H+ + Cl- ). Seldom done except in differentiation of type I and II renal tubular acidoses 10-May-16 26 ClinicalChemistry
  • 27. RENAL CONCENTRATION TEST  Voiding completely at 9 p.m. (WC)  Desmopressin administration  Collection of urine (9 p.m. – 7 a.m.)  Testing of urine osmolality in this sample (not the morning urine only  The lower limit of normal value= 950 mOsm/kg of urine  Short testing- Desmopressin, collection for 4 hours only= at least 900 mOsm/kg of urine 10-May-16 27 ClinicalChemistry
  • 28. URINALYSIS  Appearance  Specific gravity and osmolality  pH  Glucose  Protein  Urinary sediments? 10-May-16 28 ClinicalChemistry
  • 29. PROTEIN  > 2.5 g/day indicates nephrotic syndrome, Bence- Jones Protein indicates myeloma , ß2- microglobulin, small protein, filtered then absorbed by tubules, which is a sensitive test of tubular function (but also ↑ in some malignancies and inflammatory conditions). 10-May-16 29 ClinicalChemistry
  • 30. DISEASES  Nephrotic Syndrome  Acute Renal failure  Water diuresis  Osmotic diuresis 10-May-16 30 ClinicalChemistry
  • 31. NEPHROTIC SYNDROME  Increased permeability of glomerulus to proteins with proteinuria greater than 2.5 g/day with:  Edema  Hypoproteinuria  Increased serum lipids 10-May-16 31 ClinicalChemistry
  • 32. ACUTE RENAL FAILURE  Urine output <450 ml/day with a rising urea  May be:  Pre-renal failure (defect before the kidney)  Intra-renal failure (defect in the kidney e.g. acute tubular necrosis, glomerulonephritis)  Post-renal failure (defect after the kidney, e.g. prostatic enlargement, urolithiasis). 10-May-16 32 ClinicalChemistry
  • 33. ACUTE RENAL FAILURE Metabolic features:  Retention of:  Urea & creatinine  Na & water  potassium with hyper- kalaemia  Acid with metabolic acidosis Classification of Causes:  Pre-renal  reduced perfusion  Renal  inflammation  infiltration  toxicity  Post-renal  obstruction 10-May-16 33 ClinicalChemistry
  • 34. Prerenal Intrarenal Urine sodium Conc <20mmol?L >40 mmol/L Urine/plasma osmolarity ratio >1.4 <1.1 Urine/plasma urea ratio >14 <10 10-May-16 34 ClinicalChemistry
  • 35. WATER DIURESIS  urinary osmolality <200  Caused by:  Compulsive water drinking  Diabetes insipidus - neurogenic or nephrogenic 10-May-16 35 ClinicalChemistry
  • 36. OSMOTIC DIURESIS  urinary osmolality + 300  Caused by the presence of incompletely reabsorbed solutes in the tubular lumen:  Na+ - dietary, iatrogenic, diuretics, salt-losing nephritis.  Urea – CRF, recovery phase of acute tubular necrosis or post-renal failure  Glucose (diabetes mellitus)  Mannitol,and some other therapeutic agents. 10-May-16 36 ClinicalChemistry